(1S)-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol, also known as Canagliflozin, belongs to a novel therapeutic class of sodium-glucose co-transporter 2 inhibitors. US drug regulatory approval was received in march 2013 for canagliflozin (INVOKANA™) as an adjunct to diet and exercise to improve glycemic control in adults with type-2 diabetes mellitus.
U.S. Pat. No. 7,943,788 B2 first discloses canagliflozin or salts thereof and the process for its preparation.
U.S. Pat. No. 7,943,582 B2 (herein after referred as US'582) and U.S. Pat. No. 8,513,202 B2 (herein after referred as US'202) discloses crystalline form of canagliflozin hemihydrate and process for preparation thereof.
US Publication No. 2013/0237487 A1 (herein after referred as US'487 A1) discloses amorphous dapagliflozin and amorphous canagliflozin. The US'487 A1 also discloses 1:1 crystalline complex of canagliflozin with L-proline (Form CS1), ethanol solvate of a 1:1 crystalline complex of canagliflozin with D-proline (Form CS2), 1:1 crystalline complex of canagliflozin with L-phenylalanine (Form CS3), 1:1 crystalline complex of canagliflozin with D-proline (Form CS4).
The US'487 A1 discloses preparation of amorphous canagliflozin by adding toluene solution into n-heptane. After drying in vacuo the product was obtained as a white solid with melting point of 54.7° C. to 72.0° C. However, upon repetition of the said experiment, the obtained amorphous canagliflozin was having higher amount of residual solvents. Therefore, the amorphous canagliflozin obtained by process as disclosed in US'487 A1 is not suitable for pharmaceutical preparations.
The US'487 A1 further discloses that amorphous canagliflozin obtained by the above process is hygroscopic in nature which was confirmed by Dynamic vapor sorption (DVS) analysis. Further, it was observed that the amorphous form underwent a physical change between the sorption/desorption cycle, making the sorption/desorption behavior different between the two cycles. The physical change that occurred was determined to be a conversion or partial conversion from the amorphous state to a crystalline state. This change was supported by a change in the overall appearance of the sample as the humidity increased from 70% to 90% RH.
Furthermore, WO2008/069327 A1 mentions that amorphous (1S)-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol suffers from stability and handling issues such as poor filterability.
Therefore, it is evident from the prior art that the reported amorphous form of canagliflozin is unstable and hygroscopic as well as not suitable for pharmaceutical preparations due to higher amount of residual solvents above the ICH acceptable limits.
Hence, there is a need to provide a stable amorphous form of canagliflozin which is suitable for pharmaceutical preparations.
In view of the above, the present invention provides an improved process for the preparation of stable amorphous form of (1S)-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methyl phenyl]-D-glucitol which is well suitable for the pharmaceutical preparation.